The emerging spectrum of fetal acetylcholine receptor antibody-related disorders (FARAD).

In utero exposure to maternal antibodies targeting the fetal acetylcholine receptor isoform (fAChR) can impair fetal movement, leading to arthrogryposis multiplex congenita (AMC). Fetal AChR antibodies have also been implicated in apparently rare, milder myopathic presentations termed fetal acetylcholine receptor inactivation syndrome (FARIS). The full spectrum associated with fAChR antibodies is still poorly understood. Moreover, since some mothers have no myasthenic symptoms, the condition is likely underreported, resulting in failure to implement effective preventive strategies. Here we report clinical and immunological data from a multicentre cohort (n = 46 cases) associated with maternal fAChR antibodies, including 29 novel and 17 previously reported with novel follow-up data. Remarkably, in 50% of mothers there was no previously established myasthenia gravis (MG) diagnosis. All mothers (n = 30) had AChR antibodies and, when tested, binding to fAChR was often much greater than that to the adult AChR isoform. Offspring death occurred in 11/46 (23.9%) cases, mainly antenatally due to termination of pregnancy prompted by severe AMC (7/46, 15.2%), or during early infancy, mainly from respiratory failure (4/46, 8.7%). Weakness, contractures, bulbar and respiratory involvement were prominent early in life, but improved gradually over time. Facial (25/34; 73.5%) and variable peripheral weakness (14/32; 43.8%), velopharyngeal insufficiency (18/24; 75%) and feeding difficulties (16/36; 44.4%) were the most common sequelae in long-term survivors. Other unexpected features included hearing loss (12/32; 37.5%), diaphragmatic paresis (5/35; 14.3%), CNS involvement (7/40; 17.5%) and pyloric stenosis (3/37; 8.1%). Oral salbutamol used empirically in 16/37 (43.2%) offspring resulted in symptom improvement in 13/16 (81.3%). Combining our series with all previously published cases, we identified 21/85 mothers treated with variable combinations of immunotherapies (corticosteroids/intravenous immunoglobulin/plasmapheresis) during pregnancy either for maternal MG symptom control (12/21 cases) or for fetal protection (9/21 cases). Compared to untreated pregnancies (64/85), maternal treatment resulted in a significant reduction in offspring deaths (P < 0.05) and other complications, with treatment approaches involving intravenous immunoglobulin/ plasmapheresis administered early in pregnancy most effective. We conclude that presentations due to in utero exposure to maternal (fetal) AChR antibodies are more common than currently recognized and may mimic a wide range of neuromuscular disorders. Considering the wide clinical spectrum and likely diversity of underlying mechanisms, we propose 'fetal acetylcholine receptor antibody-related disorders' (FARAD) as the most accurate term for these presentations. FARAD is vitally important to recognize, to institute appropriate management strategies for affected offspring and to improve outcomes in future pregnancies. Oral salbutamol is a symptomatic treatment option in survivors.

Autopsy and pre-mortem diagnostic discrepancy review in an Irish tertiary PICU.

Our study had two objectives: (1) to review ante- and post-mortem diagnoses and assign a Goldman error classification and (2) establish autopsy rates within our centre. We performed a retrospective analysis of autopsies performed on patients who died in our paediatric intensive care unit (PICU) between November 13, 2012, and October 31, 2018. Medical and autopsy data of all patients was reviewed, and Goldman classification of discrepancy between ante- and post-mortem diagnoses was assigned. Our centre is a tertiary PICU, and we included all patients that died in PICU within the designated timeframe. Our results were as follows: 396 deaths occurred in PICU from 8329 (4.75%) admissions. Ninety-nine (25%) had an autopsy, 75 required by the coroner. All were included in the study. Fifty-three were male and 46 females. Fifty-three patients were transferred from external hospitals, 46 from our centre. Forty-one were neonates, 32 were < 1 year of age, and 26 were > 1 year of age. The median length of stay was 3 days. Eighteen were post-cardiac surgery, and three post-cardiac catheter procedure. Major diagnostic errors (class I/II) were identified in 14 (14.1%), 2 (2%) class I, and 12 (12.1%) were class II errors. Class III and IV errors occurred in 28 (28.2%) patients. Complete concordance (class V) occurred in 57 (57.5%) cases.Conclusion: We conclude that the autopsy rate and the diagnostic discrepancy rate within our PICU are comparable to those previously reported. Our findings show the continuing value of autopsy in determining the cause of death and providing greater diagnostic clarity. Given their value, post-mortem examinations, where indicated, should be considered part of a physician's duty of care to families and future patients. What is Known: • Major diagnostic discrepancies (class I/II) in PICU have been reported at 20.2%. (10) • PICU autopsy rates have varied from 36 to 67% since 1994 with most recently reported rates in 2018 being 36%. (6-9) What is New: • We report an Irish PICU major diagnostic discrepancy (class I/II) rates of 14.1% contributing further to reported discrepancy rates in PICU literature to date. • This study contributes the Irish PICU post-mortem rate in a tertiary centre which was 25% over an almost 6-year period.

Journal club: old tricks and fresh approaches.

Journal club is a long-standing pedagogy within clinical practice and education. While journal clubs throughout the world traditionally follow an established format, new approaches have emerged in recent times, including learner-centred and digital approaches. Key factors to journal club success include an awareness of the learning goals of the target audience, judicious article selection and emphasis on promoting the engagement of participant learners. This article reviews the role that journal club plays in modern clinical education and considers how to optimise its benefit for contemporary learners.

Axillary ultrasound-guided core biopsy in breast cancer: identifying higher nodal burden and more aggressive clinicopathological characteristics.

BACKGROUND: Patients with sentinel lymph node (SLN) metastases may not require axillary lymph node dissection (ALND) but it remains unclear if patients with a positive ultrasound-guided axillary core biopsy (ACB) would satisfy such criteria. AIMS: The aim of this study was to assess if breast cancer patients with a positive pre-operative ACB have more aggressive tumour characteristics/higher axillary nodal burden compared to those with a positive SLN. METHODS: Data was extracted from a prospectively maintained breast cancer database between 2012 and 2015. Patients who underwent ALND after either positive ACB or SLN were included and tumour characteristics/nodal burden were compared. RESULTS: One hundred eighty patients underwent ALND, 125/180 after positive ACB and 55/180 after positive SLNB. Patients with positive ACB were more likely to undergo mastectomy (chi-square test; p = 0.03) and have higher tumour grades (Mann-Whitney test; p < 0.01) compared to the SLNB group. Median positive nodes excised during ALND were 2 (1-22) and 1 (1-11) for ACB and SLNB groups respectively (p < 0.001). Fifty-six patients received neoadjuvant chemotherapy (NCT). Of 72/125 patients in the ACB group not receiving NCT, the median number of positive nodes was 4 (range, 1-22). Ten patients within the ACB group satisfied ACOSOG Z011 criteria. CONCLUSION: Breast cancer patients with a positive ACB are more likely to have aggressive tumour characteristics and higher nodal burden compared to those identified as having axillary nodal disease on SLNB, which may affect surgical decision making.